After damage to afferents from the hand as they course in the dorsal columns of the spinal cord, deprived portions of the brainstem cuneate nucleus, somatosensory thalamus, and somatosensory cortex become unresponsive to tactile stimuli and hand use is impaired. However, within 1 - 2 months, cortex can be reactivated by a few surviving dorsal column afferents, and hand use improves. We will evaluate the relationships between (1) the recovery of hand use, (2) the time course of the reactivation of cortex, (3) the recovery of response properties of cortical neurons, (4) the sprouting and growth of surviving dorsal column afferents in the cuneate nucleus of the lower brainstem to contact more neurons, and (5) the cellular and histochemical consequences in the cuneate nucleus of partial deafferentation. In addition, we will evaluate the effectiveness of two treatments, (6) chondroitinase ABC and (7) anti-Nogo-A, on sprouting new growth of surviving dorsal column afferents in the cuneate nucleus. The research is designed to provide an understanding of the major mechanisms of recovery of somatosensory system function after a sensory loss in humans, and to help develop favorable therapeutic approaches for humans with sensory loss after spinal cord injury. PUBLIC HEALTH RELEVANCE: The proposed research seeks to evaluate the hypothesis that a few preserved sensory afferents in the dorsal columns of the spinal cord injury can mediate the recovery of hand use by sprouting to activate a large population of neurons in the brainstem and thereby, the cortex. The proposed research will also evaluate two treatments that are likely to promote the growth of the preserved sensory afferents.